Human adenoviruses induce tumors in rodents in vivo and can also efficiently transform cells in vitro. For unexplained reasons the in vivo tumorigenic potential of different adenovirus serotypes varies over a broad range, from nontumorigenic to highly tumorigenic. The role of specific adenovirus genes in tumorigenicity will be studied by analysis of tumorigenic potential of viable recombinant viruses constructed from highly oncogenic and nonongocenic adenovirus serotypes, cells transformed by such viruses and cells transformed with cloned fragments of adenovirus DNA. The effects of specific gene products of highly oncogenic and nononcogenic adenoviruses expressed in transformed cells on interaction with host defense mechanisms, particularly cellular immunity, both natural and induced, will be analyzed. Attention also will be paid to modulation of phenotype of transformed cells during tumor development. Relationship of tumorigenic potential of transformed cells and specific parameters of their interaction with extracellular matrix will also be studied. The studies will provide clues for elucidating the mechanisms responsible for the great differences in oncogenic potential of different adenovirus serotypes in vivo.